Complexity of genome sequencing and reporting: Next generation sequencing (NGS) technologies and implementation of precision medicine in real life.

The finalization of the Human Genome Project in 2003 paved the way for a deeper understanding of cancer, favouring a faster progression towards "personalized" medicine. Research in oncology has progressively focused on the sequencing of cancer genomes, to better understand the genetic basis of tumorigenesis and identify actionable alterations to guide cancer therapy. Thanks to the development of next-generation-sequencing (NGS) techniques, sequencing of tumoral DNA is today technically easier, faster and cheaper. Commercially available NGS panels enable the detection of single or global genomic alterations, namely gene mutation and mutagenic burden, both on germline and somatic DNA, potentially predicting the response or resistance to cancer treatments. Profiling of tumor DNA is nowadays a standard in cancer research and treatment. In this review we discuss the history, techniques and applications of NGS in cancer care, under a "personalized tailored therapy" perspective.

Diagnosis of Human Immunodeficiency Virus Infection.

HIV diagnostics have played a central role in the remarkable progress in identifying, staging, initiating, and monitoring infected individuals on life-saving antiretroviral therapy. They are also useful in surveillance and outbreak responses, allowing for assessment of disease burden and identification of vulnerable populations and transmission "hot spots," thus enabling planning, appropriate interventions, and allocation of appropriate funding. HIV diagnostics are critical in achieving epidemic control and require a hybrid of conventional laboratory-based diagnostic tests and new technologies, including point-of-care (POC) testing, to expand coverage, increase access, and positively impact patient management. In this review, we provide (i) a historical perspective on the evolution of HIV diagnostics (serologic and molecular) and their interplay with WHO normative guidelines, (ii) a description of the role of conventional and POC testing within the tiered laboratory diagnostic network, (iii) information on the evaluations and selection of appropriate diagnostics, (iv) a description of the quality management systems needed to ensure reliability of testing, and (v) strategies to increase access while reducing the time to return results to patients. Maintaining the central role of HIV diagnostics in programs requires periodic monitoring and optimization with quality assurance in order to inform adjustments or alignment to achieve epidemic control.

Three atypical lethal cases associated with acute Zika virus infection in Suriname

Acute Zika virus infection usually presents with a self-limiting triad of fever, rash and arthritis. There is limited information on severe or lethal cases. We report three cases of lethal acute Zika infection, confirmed with polymerase chain reaction, in adult patients with some co-morbidities. The patients showed rapid clinical deterioration with hemorrhagic and septic shock, and exaggerated acute and innate inflammatory responses with pronounced coagulopathy, and died soon after admission to the hospital. It remains unclear whether the fatal outcomes were due to acute Zika virus infection alone or to the combination with exacerbated underlying prior disease or co-infection. Nonetheless, the severity of these cases implies that increased awareness for atypical presentations of Zika virus infection, and careful clinical assessment of patients with symptoms of Zika, is warranted during current and future outbreaks...(AU)

[Inventive activity of the Departments of Chemistry and Biochemistry of Enzymes, and Protein Structure and Function of the Palladin Institute of Biochemistry of NAS of Ukraine. Part III. Diagnostic test-systems for analysis of fibrinolysis blood system and novel approaches to thrombosis treatment].

This article continues analysis of scientific achievements of the Institute of Biochemistry in the study of hemostasis system. Two previous articles were focused on the studies of blood coagulation proteins and development of the immune-enzyme test-systems for evaluation of the risk of thrombosis upon various pathologies. This article highlights the research on the blood fibrinolysis system and new approaches to thrombosis treatment, which were developed (and are under development) in the Palladin Institute of Biochemistry of the NAS of Ukraine, in particular, in the Department of Chemistry and Biochemistry of Enzymes headed previously by Dr.Sci.(Biol.) S. O. Kudinov and now by Dr.Sci.(Biol.) T .V. Grinenko, and also in the Department of Protein Structure and Function headed by Dr.Biol.Sci. E. M. Makogonenko. The fundamental knowledge of protein molecule functions and mechanisms of regulation of blood coagulation and fibrinolysis opens up new opportunities to diagnose hemostasis disorders and control the effectiveness of the cardiovascular disease treatment and also contributes to development of new techniques for isolation of new proteins ­ promising therapeutic agents.

A century for progress in the diagnosis of Wilson disease.

The diagnosis of Wilson disease has evolved from the original description of a neurological syndrome by Wilson and other contemporaries at the turn of the 20th century to where we recognize that there is a spectrum of clinical liver and neuropsychiatric disease diagnosed by a combination of clinical and biochemical tests and more recently by molecular genetic analysis. The history of the evolution of the findings that help us establish a diagnosis of Wilson disease are presented in the following brief summary of a century of progress toward this end.

Historical perspectives in the diagnosis and treatment of primary immune deficiencies.

The field of Primary Immune Deficiency Disorders (PIDD) has advanced rapidly over the past several years with over 200 different gene mutations defined. With the recent institution of newborn screening for T cell deficiencies in many states and earlier recognition of the signs and symptoms of patients with immune deficiency, it is now apparent that PIDD is not as "rare" as was originally thought several decades ago. With the earlier recognition of patients with recurrent infections and various immune perturbations, advancements in the treatment of these immune deficiency disorders have led to enhanced survival and quality of life. In this issue, the diagnosis of PIDD through laboratory testing and skin manifestations is reviewed. The more recently described cellular immune deficiencies, selective immune deficiencies, and advances in the use of bone marrow transplantation in the correction of some of these immune deficiencies are discussed.

Translational HIV-1 research: from routine diagnostics to new virology insights in Amsterdam, the Netherlands during 1983-2013.

An HIV-1 diagnostic laboratory was established in the Academic Medical Center (AMC) of the University of Amsterdam after the discovery of human immunodeficiency virus (HIV) as the cause of the acquired immunodeficiency syndrome (AIDS). The first AIDS patients were diagnosed here in 1981 and since 1983 we have tested the samples of 50992 patients using a variety of assays that greatly improved over the years. We will describe some of the basic results from this diagnostic laboratory and then focus on the spin-off in terms of the development of novel virus assays to detect super-infections and ultra-sensitive assays to measure the intracellular HIV-1 RNA load. We also review several original research findings in the field of HIV-1 virology that stem from initial observations made in the diagnostic unit. This includes the study of genetic defects in the HIV-1 genome and time trends of the replication fitness over 30 years of viral evolution, but also the description of novel HIV-1 variants in difficult-to-diagnose clinical specimen.

Edmund Biernacki (1866-1911): Discoverer of the erythrocyte sedimentation rate. On the 100th anniversary of his death.

In contemporary medicine, the erythrocyte sedimentation rate (ESR) is used to assess severity in patients with such diseases as erysipelas, psoriasis, eosinophilic fasciitis, dermatomyositis, and Behçet's disease. We remember the scientific achievements of a Polish physician, the discoverer of the erythrocyte sedimentation rate (ESR), Edmund Faustyn Biernacki (1866-1911), on the 100th anniversary of his death. The practical application of ESR in clinical diagnostics in 1897 by Biernacki was little known for many years, because it was often neglected owing to the work of Robert Fåhraeusand Alf Westergren from 1921. In addition, it is also frequently omitted that before Westergren's and Fåhraeus's reports were published, ESR was also noticed by Ludwig Hirschfeld in 1917.

The 50-year history of the ice water test in urology.

PURPOSE: The ice water test was first described in a 1957 study of cold receptors in the bladder. We examined the role of the ice water test in the diagnosis and management of different urological conditions. MATERIALS AND METHODS: MEDLINE and PubMed literature searches were performed, spanning 1956 to January 2009. Other studies were identified by reviewing secondary references in the original citations. RESULTS: The ice water test has been shown to be a lower motoneuron segmental reflex involving C-fiber afferents, which are associated with cold receptors. A number of its clinical applications have been described. The test was first thought to be specific to upper motoneuron lesions but patients with other urological conditions have had a positive test, including those with nonneurogenic disorders. The test is almost always negative (contractions less than 15 cm H(2)O) in healthy volunteers and in patients with stress urinary incontinence, lower motoneuron conditions and bladder pain syndrome. In cases of upper motoneuron conditions the positive test rate is 46% to 92% depending on the underlying pathological condition. CONCLUSIONS: The ice water test has several potential applications but it is not needed in routine clinical practice. To date the main interest has been in patients with neurogenic bladder disorders. Further studies to investigate the validity and reliability of the ice water test in patients with idiopathic detrusor overactivity could prove useful.

[The birth of the 'diagnostic card'--on the genesis of an ,episteme' of neuroleptic efficacy in the early period of research on antipsychotic drugs in the FRG]. / Die Geburt der Stammkarte. Zur Genese eines Epistems der neuroleptischen Wirksamkeit in der frühen Psychopharmakaforschung in der BRD.

This paper describes the introduction of antipsychotic drugs in the FRG in relation to a new definition of the term ',efficacy' It focuses on problems of the standardization of clinical trials in West German psychiatry during the 1950s and 1960s. In particular, the development of a diagnostic card for the evaluation of efficacy will be discussed as part of a new experimental system and regarding its role in constructing new knowledge on neuroleptic effects.